crossing96/oncoscreening huggingface dataset:
Micropapillary bladder cancer: current treatment patterns and review of the literature.	OBJECTIVES: No guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature. MATERIALS AND METHODS: A survey developed by the Translational Science Working Group of the Bladder Cancer Advocacy Network-sponsored Think Tank meeting was distributed to members of the SUO. The results from 118 respondents were analyzed and presented with a literature review. RESULTS: Most survey respondents were urologists, with 80% considering bladder cancer their primary area of interest. Although 78% of the respondents reported a dedicated genitourinary pathologist at their institution, there were discrepant opinions on how a pathologic diagnosis of MPBC is determined as well as variability on the proportion of MPBC that is clinically significant. Among them, 78% treat MPBC differently than conventional urothelial carcinoma, with 81% reporting that they would treat cT1 MPBC with upfront radical cystectomy. However, the respondents had split opinions regarding the sensitivity of MPBC to cisplatin-based chemotherapy, which affected utilization of neoadjuvant chemotherapy in muscle-invasive disease. CONCLUSIONS: The management of MPBC is diverse among members of the SUO. Although most favors early cystectomy for cT1 MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle-invasive MPBC.	bladder
Targeting the genetic alterations of the PI3K-AKT-mTOR pathway: its potential use in the treatment of bladder cancers.	Urothelial carcinoma of the bladder is the most frequent tumor of the urinary tract and represents the fifth cause of death by cancer worldwide. The current first line chemotherapy is a combination of cisplatin and gemcitabine with median survival not exceeding 15months. Vinflunine is the only drug approved by EMEA as second-line treatment and few progresses have been made for the past 20years to increase the survival of metastatic patients, especially those who are not eligible for cisplatin-based regimen. The recent studies characterizing the genetic background of urothelial cancers of the bladder, revealed chromosomal alterations that are not seen at the same level in other types of cancers. This is especially the case for mutations of genes involved in the PI3K/AKT/mTOR signaling pathway that occupies a major place in the etiology of these tumors. Here, we describe the mutations leading to constitutive activation of the PI3K/AKT/mTOR pathway and discuss the potential use of the different classes of PI3K/AKT/mTOR inhibitors in the treatment of urothelial bladder cancers. Despite the recent pivotal study evidencing specific mutations of TSC1 in bladder cancer patients responding to everolimus and the encouraging results obtained with other derivatives than rapalogs, few clinical trials are ongoing in bladder cancers. Because of the genetic complexity of these tumors, the cross-talks of the PI3K/AKT/mTOR pathway with other pathways, and the small number of eligible patients, it will be of utmost importance to carefully choose the drugs or drug combinations to be further tested in the clinic.	bladder
Semiquantitative GATA-3 immunoreactivity in breast, bladder, gynecologic tract, and other cytokeratin 7-positive carcinomas.	OBJECTIVES: To evaluate GATA-3 immunohistochemical expression semiquantitatively in breast, gynecologic, gastric, pancreatic-biliary tract, urothelial, and vulvar/cervical squamous cell carcinomas. METHODS: GATA-3 expression was evaluated by immunohistochemistry in 198 invasive breast carcinomas on tissue microarrays. Tissue microarrays of other tissues included 144 gynecologic tumors, 28 bladder carcinomas, 63 cholangiocarcinomas, 20 pancreatic carcinomas, and 62 gastric carcinomas. Full tissue sections of 10 invasive squamous cell carcinomas were also stained. GATA-3 expression was semiquantitatively scored using an H-score method. H-score greater than 10 was considered a positive result. RESULTS: Of 186 breast carcinomas, 95% were positive (mean H-score of 217). GATA-3 expression was uncommon in 139 nonsquamous gynecologic tumors, with often weak reactivity (mean H-score <50) seen in 18% of endocervical, 7% of endometrial, and 10% of ovarian tumors. Six (60%) of 10 squamous cell carcinomas expressed GATA-3 (mean H-score of 102). Of 22 urothelial carcinomas, 95% expressed GATA-3 (mean H-score of 170). A few cholangiocarcinomas (3%), pancreatic adenocarcinomas (10%), and gastric carcinomas (2%) weakly expressed GATA-3 (mean H-score <50). CONCLUSIONS: Strong GATA-3 expression is a reliable marker of primary breast carcinoma in the appropriate clinical context. GATA-3 reactivity in around 70% of triple-negative breast carcinomas is also clinically useful. Significant reactivity in gynecologic squamous cell carcinomas suggests that GATA-3 alone cannot reliably distinguish these tumors from urothelial carcinoma.	bladder
Synchronous bladder and prostate cancers in the specimens of radical cystoprostatectomy: a multicenter retrospective analysis.	The purpose of this study was to evaluate the features of prostate cancer that have been incidentally detected in radical cystoprostatectomy specimens of bladder cancer patients. The researchers of the current study retrospectively evaluated the data from 119 men who underwent radical cystoprostatectomy at four referral institutions in Ankara, Turkey. Of the 21 prostate cancer patients, 17 (81%) were aged ≥ 60 years; 10 (47.6%) had clinically significant diseases; three had a Gleason score of 6, three had a Gleason score of 7, three had a Gleason score of 8, one had a positive surgical margin along with extracapsular invasion of the tumor and a high Gleason score, and three patients had a tumor volume of ≥ 0.5 cm(3), of which two also had a high Gleason score. Patients were followed-up for a mean of 29 ± 10.2 months; the overall survival was 96.6% (n = 115) during that period. Preoperative digital rectal examination and prostate-specific antigen values did not differ between the benign and prostate cancer groups. There was no survival advantage in the insignificant prostate cancer and benign prostate groups. No additional benefit for predicting prostate cancer was found with digital rectal examination and prostate-specific antigen tests, although some clinicians advised such. In patients aged < 60 years, organ-sparing cystectomy seems reasonable. In prostate-sparing surgery, candidates who are aged >60 years, the preoperative work-up may routinely include prostate biopsy, especially the apex. Preoperative findings of multifocality of bladder cancers and the presence of carcinoma in situ have the risk of prostatic involvement.	bladder
External validation of a multiplex urinary protein panel for the detection of bladder cancer in a multicenter cohort.	BACKGROUND: Because of the faltering sensitivity and/or specificity, urine-based assays currently have a limited role in the management of patients with bladder cancer. The aim of this study was to externally validate our previously reported protein biomarker panel from multiple sites in the United States and Europe. METHODS: This multicenter external validation study included a total of 320 subjects (bladder cancer = 183). The 10 biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SDC1, and SERPINE1) were measured using commercial ELISA assays in an external laboratory. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values. RESULTS: Utilizing the combination of all 10 biomarkers, the area under the ROC for the diagnostic panel was noted to be 0.847 (95% confidence interval, 0.796-0.899), outperforming any single biomarker. The multiplex assay at optimal cutoff value achieved an overall sensitivity of 0.79, specificity of 0.79, positive prediction value of 0.73, and negative prediction value of 0.84 for bladder cancer classification. Sensitivity values of the diagnostic panel for high-grade bladder cancer, low-grade bladder cancer, muscle invasive bladder cancer, and non-muscle invasive bladder cancer were 0.81, 0.90, 0.95, and 0.77, respectively. CONCLUSIONS: Urinary levels of the biomarker panel enabled discrimination of patients with bladder cancer and controls, and the levels of biomarker subsets were associated with advancing tumor grade and stage. IMPACT: If proven to be reliable, urinary diagnostic biomarker assays can detect bladder cancer in a timely manner such that the patient can expect improvements in overall survival and quality of life.	bladder
Solitary cystic cerebellar metastasis in a patient with invasive transitional cell carcinoma of the bladder.	Transitional cell carcinoma of the bladder (TCC) represents nearly 90% of genitourinary malignancies and typically presents with locally invasive symptoms. Metastasis to the central nervous system (CNS) is uncommon occurring in <5% of patients. When present, metastatic lesions are typically solid, isolated and located in the cerebrum. We report a case of a patient with a history of TCC who presented with lethargy and ataxia and was found to have a solitary cystic cerebellar lesion consistent with metastatic disease. Unfortunately, the prognosis for patients with TCC and CNS metastases is poor. Treatment options include debulking surgery, whole brain radiation, stereotactic radiosurgery and chemotherapy. Unfortunately, treatment may not appreciably extend survival and care is often supportive in previously reported cases. Though uncommon, TCC can metastasise to the CNS and should be considered in the differential diagnosis of patients, particularly those who were treated with aggressive surgery or combination chemotherapy previously.	bladder
Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.	BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated. METHODS: A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan-Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR. RESULTS: The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR. CONCLUSIONS: Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.	bladder
Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer.	The aim of this study was to test the utility of AIMP3, an upstream regulator of DNA damage response following genotoxic stress, as a clinical biomarker in muscle-invasive bladder cancer (MIBC). AIMP3 was identified from a meta-analysis of a global gene-expression dataset. AIMP3 protein expression was determined by immunohistochemistry on a customised bladder cancer tissue-microarray (TMA). The mechanism of gene silencing was probed using methylation-specific PCR. The association between AIMP3 expression, Tp53 transactivity and genomic stability was analysed. In vitro AIMP3 translocation to the nucleus in response to ionising radiation was demonstrated using immunofluorescence. Radiosensitisation effects of siRNA-mediated AIMP3-knockdown were measured using colony forming assays. TMAs derived from patients enrolled in BCON, a Phase III multicentre radiotherapy trial in bladder cancer (ISRCTN45938399) were used to evaluate the association between AIMP3 expression and survival. The prognostic value of AIMP3 expression was determined in a TMA derived from patients treated by radical cystectomy. Loss of AIMP3 expression was frequent in MIBC and associated with impaired Tp53 transactivity and genomic instability. AIMP3-knockdown was associated with an increase in radioresistance. Loss of AIMP3 expression was associated with survival in MIBC patients following radiotherapy (HR = 0.53; 95% CI: 0.36 to 0.78, p = 0.002) but was not prognostic in the cystectomy set. In conclusion, AIMP3 expression is lost in a subset of bladder cancers and is significantly predictive of survival following radiotherapy in MIBC patients.	bladder
Eosinophilia in routine blood samples as a biomarker for solid tumor development - A study based on the Copenhagen Primary Care Differential Count (CopDiff) Database.	BACKGROUND: Eosinophilia may represent an early paraclinical sign of malignant disease and a host anti-tumor effect. The association between eosinophilia and the development of solid tumors has never before been examined in an epidemiological setting. The aim of the present study was to investigate eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (< 0.5 × 10(9)/l), mild (≥ 0.5-1.0 × 10(9)/l) or severe (≥ 1.0 × 10(9)/l) eosinophilia. From the Danish Civil Registration System and the Danish Cancer Registry we ascertained all-cause death and solid tumors within the first three years following the DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for previous eosinophilia, sex, age, year, month, C-reactive protein, previous cancer and Charlson's Comorbidity Index. RESULTS: The risk of bladder cancer was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. CONCLUSION: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution.	bladder
The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells.	BACKGROUND: Activation of Rho, one of the small GTPases, and its major downstream target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We previously showed that elevation of Rho and ROCK expression was associated with tumor invasion, metastasis, and an unfavorable prognosis in patients with urothelial cancer of the bladder or upper urinary tract. METHODS: We investigated the effects of a ROCK inhibitor on the growth, migration, and apoptosis of bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by measuring its GTP-bound active form and assessed the expression of ROCK to explore the underlying molecular mechanisms. RESULTS: Lysophosphatidic acid (LPA) and geranylgeraniol (GGOH) induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation and migration, and also induced apoptosis in a dose-dependent manner. HA-1077 dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity. CONCLUSIONS: These findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.	bladder
Risk factors of hospital readmission after radical cystectomy and urinary diversion: analysis of a large contemporary series.	OBJECTIVES: To determine the incidence, risk factors and causes of hospital readmission in a large series of patients who underwent radical cystectomy (RC) and urinary diversion. PATIENTS AND METHODS: We retrospectively analysed the data of 1000 patients who underwent RC and urinary diversion between January 2004 and September 2009 in our tertiary referral centre. Patients stayed in hospital for 21 and 11 days for orthotopic and ileal conduit diversions, respectively. The primary outcome was the development of a complication requiring hospital readmission at ≤3 months (early) and >3 months (late). Causes of hospital readmissions were categorised according to frequency of readmissions. Predictors were determined using univariate and multivariate logistic regression models. RESULTS: In all, 895 patients were analysed excluding 105 patients because of perioperative mortality and loss to follow-up. Early and late readmissions occurred in 8.6% and 11% patients, respectively. The commonest causes of first readmission were upper urinary tract obstruction (UUO, 13%) and pyelonephritis (12.4%) followed by intestinal obstruction (11.9%) and metabolic acidosis (11.3%). The development of postoperative high-grade complications (odds ratio [OR] 1.955; 95% confidence interval [CI] 1.254-3.046; P = 0.003) and orthotopic bladder substitution (OR 1.585; 95% CI 1.095-2.295; P = 0.015) were independent predictors for overall hospital readmission after RC. Postoperative high-grade complications (OR 2.488; 95% CI 1.391-4.450; P = 0.002), orthotopic bladder substitution (OR 2.492; 95% CI 1.423-4.364; P = 0.001) and prolonged hospital stay (OR 1.964; 95% CI:1.166-3.308; P = 0.011) were independent predictors for early readmission while hypertension (OR 1.670; 95% CI 1.007-2.769; P = 0.047) was an independent predictor for late readmission. CONCLUSION: Hospital readmissions are a significant problem after RC. In the present study, UUO, pyelonephritis, metabolic acidosis and intestinal obstruction were the main causes of readmission. Orthotopic bladder substitution and development of postoperative high-grade complications were significant predictors for overall readmission.	bladder
Urachal cancer with direct caecal invasion: differential diagnosis from primary colon cancer.	A 56-year-old man who had a history of repeated previous treatment for cystitis was admitted with abdominal distension, dysuria, pollakiuria, nocturia and sensation of urine retention after emptying the bladder. A CT scan showed a 10 cm irregularly shaped soft tissue mass abutting the anterosuperior aspect of the urinary bladder with wall thickening and a soft tissue component in the caecum. Colonoscopy revealed an encircling huge fungating mass on the caecum. The tumour was removed surgically. Histological examination showed moderately differentiated adenocarcinoma extending to the caecal wall and the bladder mucosa, the origin of the mass was consistent with that of a urachal cyst. The epicentre of the tumour was located in the bladder wall, with a distinct margin as a pathological feature. The patient was diagnosed with urachal cancer and concurrent direct caecal invasion.	bladder
Identification of different phenotypes of interstitial cells in the upper and deep lamina propria of the human bladder dome.	PURPOSE: There is increasing evidence for an important role of the lamina propria in bladder physiology and interstitial cells seem to have a key role in this area. Interstitial cells in the upper lamina propria have been studied most frequently. We characterized interstitial cells in the deeper lamina propria and hypothesized that the 2 interstitial cell populations have different phenotypes based on their ultrastructural and immunohistochemical properties. MATERIALS AND METHODS: Tissue samples were obtained from macroscopically and microscopically normal areas of radical cystectomy specimens. A panel of immunohistochemical markers was used to characterize lamina propria interstitial cells. Single/double immunohistochemistry/immunofluorescence was performed. At a second phase electron microscopy was used to compare upper and deeper lamina propria interstitial cells. RESULTS: Overall the phenotype of upper lamina propria interstitial cells was vimentin, α-smooth muscle actin, caveolin-1 and 2, PDGFRα, and nonphosphorylated and phosphorylated connexin 43 positive, and CD34 and c-kit negative. The overall phenotype of deeper lamina propria interstitial cells was vimentin, CD34 and nonphosphorylated connexin 43 positive, and α-smooth actin, caveolin-1 and 2, PDGFRα, phosphorylated connexin 43 and c-kit negative. Based on ultrastructural findings upper lamina propria interstitial cells were fibroblasts with myoid features and sparse myofibroblasts while deeper lamina propria interstitial cells were interstitial cell of Cajal-like cells. CONCLUSIONS: To our knowledge this is the first study of 2 main interstitial cell populations in the upper and deeper lamina propria of the human bladder with distinct ultrastructural and immunohistochemical phenotypes. Future research is needed to elucidate whether these morphological findings reflect different roles for upper and deeper lamina propria interstitial cells in bladder physiology.	bladder